Nipah Virus (NiV) at the Human-Animal-Environment Interface: Emerging Insights into Spillover Dynamics, Neurotropism, and Future Pandemic Risk
Abstract
Nipah virus (NiV), a highly pathogenic member of the Henipavirus genus within the Paramyxoviridae family, continues to represent a critical zoonotic threat at the intersection of humans, animals, and the environment. First identified in Malaysia in 1998, NiV has since emerged as a paradigm of viral spillover driven by ecological disruption and anthropogenic activities. This review elucidates contemporary insights into the complex interplay governing NiV transmission dynamics, molecular neurotropism, and its potential to precipitate future pandemics. The spillover of NiV from its natural reservoir, Pteropus fruit bats, to intermediate hosts such as pigs, and ultimately to humans, is profoundly influenced by habitat fragmentation, agricultural intensification, and climate-induced alterations in bat foraging behavior. At the molecular level, NiV exhibits pronounced neurotropism and vasculotropism mediated through its interaction with ephrin-B2 and ephrin-B3 receptors, leading to widespread endothelial infection, microvascular damage, and neuronal dysfunction that culminate in fatal encephalitis. Moreover, the virus demonstrates immune evasion strategies that suppress interferon signaling, thereby facilitating systemic dissemination. Despite its high case fatality rate and recurrent outbreaks in South and Southeast Asia, the absence of licensed antiviral therapies or vaccines underscores the urgency of advancing translational research and cross-sectoral surveillance frameworks. The convergence of ecological perturbations, viral adaptability, and limited healthcare infrastructure in endemic regions amplifies the likelihood of future spillover and sustained human-to-human transmission. A unified One Health approach integrating virological, ecological, and epidemiological disciplines is imperative to mitigate NiV’s pandemic potential and to strengthen global preparedness against emerging zoonoses.
Keywords: Neurotropism, Nipah virus (NiV), One Health, Pandemic preparedness, Spillover dynamics, Zoonotic transmission.
Keywords:
Neurotropism, Nipah virus (NiV), One Health, Pandemic preparedness, Spillover dynamics, Zoonotic transmissionDOI
https://doi.org/10.22270/jddt.v15i11.7457References
1. Dewangan V, Sahu R, Satapathy T, Roy A. The exploring of current development status and the unusual symptoms of corona virus pandemic (Covid-19). Research journal of Pharmacology and Pharmacodynamics. 2020; 12(4):172-6. https://doi.org/10.5958/2321-5836.2020.00031.2
2. Gazal S, Sharma N, Gazal S, Tikoo M, Shikha D, Badroo GA, Rashid M, Lee SJ. Nipah and Hendra viruses: deadly zoonotic paramyxoviruses with the potential to cause the next pandemic. Pathogens. 2022 Nov 25;11(12):1419. https://doi.org/10.3390/pathogens11121419
3. Khan S, Akbar SM, Al Mahtab M, Uddin MN, Rashid MM, Yahiro T, Hashimoto T, Kimitsuki K, Nishizono A. Twenty-five years of Nipah outbreaks in Southeast Asia: A persistent threat to global health. IJID regions. 2024 Dec 1;13:100434. https://doi.org/10.1016/j.ijregi.2024.100434
4. Anish TS, Aravind R, Radhakrishnan C, Gupta N, Yadav PD, Cherian JJ, Sahay R, Chenayil S, AS AK, Moorkoth AP, Ashadevi. Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: lessons from Kerala, India. PLOS Global Public Health. 2024 Dec 19;4(12):e0003926. https://doi.org/10.1371/journal.pgph.0003926
5. Thankachy S, Amju KP, Mathew J, Moosan H, Rahi M, Kuttiatt VS. Emergence of West Nile virus infection in Kerala, South India: A case of concern. Journal of Vector Borne Diseases. 2025 Jul 1;62(3):274-8. https://doi.org/10.4103/jvbd.jvbd_172_24
6. Anish TS, Aravind R, Radhakrishnan C, Gupta N, Yadav PD, Cherian JJ, Sahay R, Chenayil S, AS AK, Moorkoth AP, Ashadevi. Pandemic potential of the Nipah virus and public health strategies adopted during outbreaks: lessons from Kerala, India. PLOS Global Public Health. 2024 Dec 19;4(12):e0003926. https://doi.org/10.1371/journal.pgph.0003926
7. Devadharshini K, Vanmathi A, Mohanadasse NQ, Rajaa KD. Monkeypox: A resurgent zoonotic threat in the post-pandemic era. IJBS. 2025;7(8):16-25. https://doi.org/10.33545/26649926.2025.v7.i8a.435
8. Vasudevan SS, Subash A, Mehta F, Kandrikar TY, Desai R, Khan K, Khanduja S, Pitliya A, Raavi L, Kanagala SG, Gondaliya P. Global and regional mortality statistics of nipah virus from 1994 to 2023: a comprehensive systematic review and meta-analysis. Pathogens and Global Health. 2024 Aug 17;118(6):471-80. https://doi.org/10.1080/20477724.2024.2380131
9. Vasudevan SS, Subash A, Mehta F, Kandrikar TY, Desai R, Khan K, Khanduja S, Pitliya A, Raavi L, Kanagala SG, Gondaliya P. Global and regional mortality statistics of nipah virus from 1994 to 2023: a comprehensive systematic review and meta-analysis. Pathogens and Global Health. 2024 Aug 17;118(6):471-80. https://doi.org/10.1080/20477724.2024.2380131
10. Sazzad HM, Hossain MJ, Gurley ES, Ameen KM, Parveen S, Islam MS, Faruque LI, Podder G, Banu SS, Lo MK, Rollin PE. Nipah virus infection outbreak with nosocomial and corpse-to-human transmission, Bangladesh. Emerging infectious diseases. 2013 Feb;19(2):210. DOI: https://doi.org/10.3201/eid1902.120971
11. Bruno L, Nappo MA, Ferrari L, Di Lecce R, Guarnieri C, Cantoni AM, Corradi A. Nipah virus disease: epidemiological, clinical, diagnostic and legislative aspects of this unpredictable emerging zoonosis. Animals. 2022 Dec 31;13(1):159. https://doi.org/10.3390/ani13010159
12. Safdar M, ur Rehman S, Younus M, Rizwan MA, Kaleem M, Ozaslan M. One Health approach to Nipah virus prevention. Vacunas (English Edition). 2024 Apr 1;25(2):264-73. https://doi.org/10.1016/j.vacune.2024.05.014
13. White RJ, Razgour O. Emerging zoonotic diseases originating in mammals: a systematic review of effects of anthropogenic land‐use change. Mammal review. 2020 Oct;50(4):336-52. https://doi.org/10.1111/mam.12201
14. Glennon EE. Spillover and emergence of bat-origin viral infections. University of Cambridge (United Kingdom); 2021. DOI: https://doi.org/10.17863/CAM.72070
15. Wong S, Lau S, Woo P, Yuen KY. Bats as a continuing source of emerging infections in humans. Reviews in medical virology. 2007 Mar;17(2):67-91. https://doi.org/10.1002/rmv.520
16. Shanta IS, Luby SP, Hossain K, Heffelfinger JD, Kilpatrick AM, Haider N, Rahman T, Chakma S, Ahmed SS, Sharker Y, Pulliam JR. Human exposure to bats, rodents and monkeys in Bangladesh. EcoHealth. 2023 Mar;20(1):53-64. DOI : https://doi.org/10.1007/s10393-023-01628-9
17. Tan FH, Sukri A, Idris N, Ong KC, Schee JP, Tan CT, Tan SH, Wong KT, Wong LP, Tee KK, Chang LY. A systematic review on Nipah virus: global molecular epidemiology and medical countermeasures development. Virus Evolution. 2024;10(1):veae048. https://doi.org/10.1093/ve/veae048
18. Yadav PD, Baid K, Patil DY, Shirin T, Rahman MZ, Peel AJ, Epstein JH, Montgomery JM, Plowright RK, Salje H, Gurley ES. A One Health approach to understanding and managing Nipah virus outbreaks. Nature microbiology. 2025 May 28:1-0. https://doi.org/10.1038/s41564-025-02020-9
19. Gazal S, Sharma N, Gazal S, Tikoo M, Shikha D, Badroo GA, Rashid M, Lee SJ. Nipah and Hendra viruses: deadly zoonotic paramyxoviruses with the potential to cause the next pandemic. Pathogens. 2022 Nov 25;11(12):1419. https://doi.org/10.3390/pathogens11121419
20. Samad MA. A REVIEW OF EMERGING AND RE-EMERGING ZOONOTIC VIRAL DISEASES OVER FIFTY-EIGHT YEARS WITH A ‘ONE HEALTH’PERSPECTIVE IN BANGLADESH. DOI: https://doi.org/10.36111/jvmohr.2025.7(1-2).0041
21. McLean RK, Graham SP. The pig as an amplifying host for new and emerging zoonotic viruses. One Health. 2022 Jun 1;14:100384. McLean RK, Graham SP. The pig as an amplifying host for new and emerging zoonotic viruses. One Health. 2022 Jun 1; 14:100384. https://doi.org/10.1016/j.onehlt.2022.100384
22. Mohana Murugan AV. Understanding vertebrate-pathogen co-evolution using state-of-the-art glycomics. 2023-06-05. https://doi.org/10.25904/1912/4927
23. Escudero-Pérez B, Lalande A, Mathieu C, Lawrence P. Host–Pathogen interactions influencing zoonotic spillover potential and transmission in humans. Viruses. 2023 Feb 22;15(3):599. https://doi.org/10.3390/v15030599
24. Vashisht V, Vashisht A, Mondal AK, Farmaha J, Alptekin A, Singh H, Ahluwalia P, Srinivas A, Kolhe R. Genomics for emerging pathogen identification and monitoring: Prospects and obstacles. Biomed Informatics. 2023 Dec 7;3(4):1145-77. https://doi.org/10.3390/biomedinformatics3040069
25. de Boer EC, van Gils JM, van Gils MJ. Ephrin-Eph signaling usage by a variety of viruses. Pharmacological research. 2020 Sep 1; 159:105038. https://doi.org/10.1016/j.phrs.2020.105038
26. Vezzani A, Fujinami RS, White HS, Preux PM, Blümcke I, Sander JW, Löscher W. Infections, inflammation and epilepsy. Acta neuropathologica. 2016 Feb;131(2):211-34. https://doi.org/10.1007/s00401-015-1481-5
27. Li YX, Wang HB, Li J, Jin JB, Hu JB, Yang CL. Targeting pulmonary vascular endothelial cells for the treatment of respiratory diseases. Frontiers in pharmacology. 2022 Aug 30; 13: 983816. https://doi.org/10.3389/fphar.2022.983816
28. Al-Obaidi MM, Muthanna A, Desa MN. Nipah Virus neurotropism: insights into blood-brain barrier disruption. Journal of Integrative Neuroscience. 2024 Apr 29;23(5):90. https://doi.org/10.31083/j.jin2305090
29. Robinson CP, Busl KM. Neurologic manifestations of severe respiratory viral contagions. Critical care explorations. 2020 Apr 1; 2(4):e0107. https://doi.org/10.1097/CCE.0000000000000107
30. Becker N, Maisner A. Nipah virus impairs autocrine IFN signaling by sequestering STAT1 and STAT2 into inclusion bodies. Viruses. 2023 Feb 17;15(2):554. https://doi.org/10.3390/v15020554
31. Dai J, Zhou P, Li S, Qiu HJ. New insights into the crosstalk among the interferon and inflammatory signaling pathways in response to viral infections: defense or homeostasis. Viruses. 2022 Dec 15;14(12):2798. https://doi.org/10.3390/v14122798
32. Kumar R. Understanding and managing acute encephalitis. F1000Research. 2020 Jan 29;9:F1000-aculty. DOI: https://doi.org/10.12688/f1000research.20634.1
33. Hilleman MR. Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections. Proceedings of the National Academy of Sciences. 2004 Oct 5;101(suppl_2):14560-6. https://doi.org/10.1073/pnas.0404758101
34. Cioboata R, Balteanu MA, Osman A, Vlasceanu SG, Zlatian OM, Mitroi DM, Catana OM, Socaci A, Tieranu EN. Coinfections in Tuberculosis in Low-and Middle-Income Countries: Epidemiology, Clinical Implications, Diagnostic Challenges, and Management Strategies-A Narrative Review. Journal of Clinical Medicine. 2025 Mar 21;14(7):2154. DOI: https://doi.org/10.3390/jcm14072154
35. Salimi H, Cain MD, Klein RS. Encephalitic arboviruses: emergence, clinical presentation, and neuropathogenesis. Neurotherapeutics. 2016 Jun 1;13(3):514-34. https://doi.org/10.1007/s13311-016-0443-5
36. Satapathy T, Satapathy A, Satapathy A, Yadav N, Chandrakar M, Chandrakar K. Recent outbreaks of Human Metapneumovirus (HMPV): Prevention, Diagnosis and Therapeutic insights. Journal of Drug Delivery & Therapeutics. 2025; 15(2):193-203. doi: https://doi.org/10.22270/jddt.v15i2.7000
37. Yadav A, Singh V. Strengthening Public Health Systems to Combat the Rising Threat of Nipah Virus: A Call for Global Preparedness and Response. https://doi.org/10.1007/5584_2024_836
38. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Reviews in medical virology. 2006 Jan;16(1):37-48. https://doi.org/10.1002/rmv.483
39. Satapathy A, Yadav N, Satapathy T, Sen K, Sahu S, Gupta A, Pradhan B, Bhardwaj S. H9N2: A Mysterious Avian Influenza Virus: A Global Threat for Respiratory Pneumonia. Research Journal of Pharmacology and Pharmacodynamics. 2024; 16(2):127-133. doi: https://doi.org/10.52711/2321-5836.2024.00023
40. Konstantinova ID, LAndronova V, Fateev IV, Esipov RS. Favipiravir and its structural analogs: Antiviral activity and synthesis methods. Acta naturae. 2022 Apr;14(2):16.DOI: https://doi.org/10.32607/actanaturae.11652
41. Lv C, He J, Zhang Q, Wang T. Vaccines and Animal Models of Nipah Virus: Current Situation and Future Prospects. Vaccines. 2025 Jun 4;13(6):608.doi: https://doi.org/10.3390/vaccines13060608
42. Tang J, Amin MA, Campian JL. Past, Present, and Future of Viral Vector Vaccine Platforms: A Comprehensive Review. Vaccines. 2025 May 15;13(5):524.https://doi.org/10.3390/vaccines13050524
43. Gupta A, Satapathy T, Pradhan B, Sen K, Sahu S, Sahu AK, Bhardwaj SK, Khan MA. Experimental Animal Models for Influenza/Flu Virus Vaccine Development. Journal of Drug Delivery and Therapeutics. 2024; 14(2):192-204. doi: https://doi.org/10.22270/jddt.v14i2.6362
44. Rolnick D, Donti PL, Kaack LH, Kochanski K, Lacoste A, Sankaran K, Ross AS, Milojevic-Dupont N, Jaques N, Waldman-Brown A, Luccioni AS. Tackling climate change with machine learning. ACM Computing Surveys (CSUR). 2022 Feb 8;55(2):1-96. https://doi.org/10.1145/3485128
45. Schroader JH, Handley MT, Reddy K. Inosine triphosphate pyrophosphatase: A guardian of the cellular nucleotide pool and potential mediator of RNA function. Wiley Interdisciplinary Reviews: RNA. 2023 Sep;14(5):e1790. https://doi.org/10.1002/wrna.1790
46. Wu J, Wang X, Liu Q, Lu G, Gong P. Structural basis of transition from initiation to elongation in de novo viral RNA-dependent RNA polymerases. Proceedings of the National Academy of Sciences. 2023 Jan 3; 120(1):e2211425120. https://doi.org/10.1073/pnas.2211425120
47. Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad-spectrum inhibitor of viral RNA polymerase. Proceedings of the Japan Academy, Series B. 2017 Aug 2;93(7):449-63. https://doi.org/10.2183/pjab.93.027
48. Sajjad A, Haq I, Syed R, Anwar F, Hamza M, Musharaf M, Kiani T, Nouroz F. In-silico molecular analysis and blocking of the viral G protein of Nipah virus interacting with ephrin B2 and B3 receptor by using peptide mass fingerprinting. Frontiers in Bioinformatics. 2025 Jun 25;5:1526566.DOI: https://doi.org/10.3389/fbinf.2025.1526566
49. Mehnaz S, Anjum R, Mithila FR, Dewan SM, Islam MR. The Current Pathogenicity and Potential Risk Assessment of Nipah Virus as Potential Cause of “Disease X”: A Narrative Review. Health Science Reports. 2024 Dec; 7(12):e70241. https://doi.org/10.1002/hsr2.70241
50. Kamalrathne T, Amaratunga D, Haigh R, Kodituwakku L. Need for effective detection and early warnings for epidemic and pandemic preparedness planning in the context of multi-hazards: Lessons from the COVID-19 pandemic. International journal of disaster risk reduction. 2023 Jun 15; 92:103724. https://doi.org/10.1016/j.ijdrr.2023.103724
51. Saylors K, Wolking DJ, Hagan E, Martinez S, Francisco L, Euren J, Olson SH, Miller M, Fine AE, Thanh NN, Tran Minh P. Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats. One Health Outlook. 2021 May 14;3(1):11. https://doi.org/10.1186/s42522-021-00036-9
52. Johnson T, Jamrozik E, Hurst T, Cheah PY, Parker MJ. Ethical issues in Nipah virus control and research: addressing a neglected disease. Journal of medical ethics. 2024 Sep 1; 50(9):612-7. https://doi.org/10.1136/jme-2023-109469
53. Olorunsogo TO, Ogugua JO, Muonde M, Maduka CP, Omotayo O. Environmental factors in public health: A review of global challenges and solutions. World Journal of Advanced Research and Reviews. 2024;21(1):1453-66. https://doi.org/10.30574/wjarr.2024.21.1.0176
54. Bruno L, Nappo MA, Ferrari L, Di Lecce R, Guarnieri C, Cantoni AM, Corradi A. Nipah virus disease: epidemiological, clinical, diagnostic and legislative aspects of this unpredictable emerging zoonosis. Animals. 2022 Dec 31;13(1):159. https://doi.org/10.3390/ani13010159
55. Borrajo A, Svicher V, Salpini R, Pellegrino M, Aquaro S. Crucial role of central nervous system as a viral anatomical compartment for HIV-1 infection. Microorganisms. 2021 Dec 8; 9(12):2537. https://doi.org/10.3390/microorganisms9122537
56. Ma J, Guo Y, Gao J, Tang H, Xu K, Liu Q, Xu L. Climate change drives the transmission and spread of vector-borne diseases: an ecological perspective. Biology. 2022 Nov 7;11(11):1628. https://doi.org/10.3390/biology11111628
57. Mardini A, Shaykhon N, Khan A, Mardini A, Saeed HN. Global disparities in access to vaccine clinical trials: a review of the literature. Vaccines. 2024 Mar 23; 12(4):348. https://doi.org/10.3390/vaccines12040348
58. Yadav PD, Baid K, Patil DY, Shirin T, Rahman MZ, Peel AJ, Epstein JH, Montgomery JM, Plowright RK, Salje H, Gurley ES. A One Health approach to understanding and managing Nipah virus outbreaks. Nature microbiology. 2025 May 28:1-0. https://doi.org/10.1038/s41564-025-02020-9.
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